This proposal explores the neural mechanisms underlying motivational control of reward-seeking behavior by reward-paired stimuli, and their modulation by exposure to drugs of abuse. Specifically, this proposal examines the involvement of the extracellular-signal regulated kinase (ERK) pathway in the Nucleus Accumbens core (NAcc) in cue-controlled behavior, and how exposure to one abused substance, the psychostimulant d-amphetamine, may alter cue-controlled behavior by altering NAcc ERK signaling. It is hypothesized that NAcc ERK signaling is necessary for reward-paired stimuli to motivate reward-seeking behavior. Furthermore, d-amphetamine exposure is hypothesized to enhance cue-controlled behavior by increasing NAcc ERK activation in response to reward-paired stimuli. The proposed experiments use Pavlovian and instrumental learning tasks coupled with intracranial infusions of an ERK antagonist to assess the role of NAcc ERK signaling in cue-induced reward seeking. The effect of d-amphetamine exposure on cue-induced reward seeking and cue-evoked ERK activation will be assessed using Western blot analysis. These experiments may shed light on the mechanisms underlying relapse caused by drug-paired cues. [unreadable] [unreadable] [unreadable]